(671b) Polymer Nanoparticle Synthesis and Characterization for the Delivery of Osteoinductive Molecules

Authors: 
Wechsler, M. E., The University of Texas at Austin
Culver, H. R., The University of Texas at Austin
Peppas, N. A., University of Texas at Austin
Localized delivery of osteoinductive factors (e.g., growth factors, peptides, and small molecules) remains a major challenge in bone tissue engineering to promote regeneration and repair of damaged tissues. Delivery of select bone morphogenetic proteins (BMPs) has shown great therapeutic potential (specifically, BMP-2 and BMP-7). However, current delivery methods require supraphysiological concentrations to obtain desired effects and experience inadequate retention at the site of delivery. In contrast, the use of small molecules to induce bone regeneration has not been fully explored and displays several advantages over the use of growth factors (including small size, high stability and non-immunogenicity). Local administration of osteoinductive small molecules can be achieved through incorporation within osteoconductive materials, such as, bone tissue engineered scaffolds. However, optimal carriers for small molecule delivery within these scaffolds remain partially unknown. For this purpose, polymer nanoparticles were synthesized and characterized for the delivery of osteoinductive small molecules. Nanogels were synthesized via solution polymerization. N-isopropylacrylamide (NIPAM) was co-polymerized with methacrylic acid (MAA) and either benzyl methacrylate (BZMA) or 2-hydroxyethyl methacrylate (HEMA) at varying concentrations using N,Nâ??-methylenebisacrylamide as the crosslinker. Synthesis of P(NIPAM-co-MAA-co-BZMA) and P(NIPAM-co-MAA-co-HEMA) nanogels was confirmed by Fourier transform infrared spectroscopy. Nanoparticle size was determined using dynamic light scattering. Results show successful synthesis of the desired polymer formulations at varying monomer concentrations. Thus, nanogels can be further used to investigate the load and release of small osteoinductive molecules. Successful delivery of these molecules within tissue engineered constructs could have major impact in bioengineering and in specific therapeutic modalities in the clinical milieu.